Baby Bottle Chemical

30 July 2007: A just-published study is offering some good news and bad news about a controversial chemical found in some of the food and beverage containers you may have in your home. As this ScienCentral News video explains, the study reveals a new way the chemical might be harmful to developing fetuses and young children. They also found that some dietary supplements can reverse its effects.

Controversial Chemical

Many email users are familiar with the scary hoax messages warning of the dangers of dishwashing, re-using, microwaving or leaving plastic bottles in the car. But as more studies are published on the effects of low doses of bisphenol A -- an integral part of hard, clear plastic baby bottles, water cooler dispensers, and linings for canned foods — the truth about some plastics is starting to raise some real concern.

Because small amounts of bisphenol A can leach into foods and beverages, some cities and states have tried to ban it from products used by infants and children. It belongs to a class of chemicals called endocrine disruptors that can mimic hormones that affect reproduction and metabolism. Bisphenol A is largely used in polycarbonate plastics, which is identified by a recycling symbol with the number 7 inside.

Now new research on a type of mice whose coat color displays their disease susceptibility reveals that low doses of the chemical can contribute to diseases like obesity and cancer.

"This will change completely the way people look at endocrine disruptors, not only from the standpoint of toxicology assessments of different other compounds and their risks, for example, to humans," says Duke University's Randy Jirtle. "But also, maybe potentially to block these effects in humans."

Jirtle and his team were the first to show that mice with identical genes could develop into very different-looking animals, with very different health prospects, depending on whether their mothers' diet while pregnant included certain nutritional supplements.

"If the animals [the offspring] are brown, they're lean and clean and don't get diseases all the way up until the end of their life, whereas if the animals are yellow they have a high propensity to become obese, have diabetes and develop cancer," says Jirtle. The group proved that the differences are caused by epigenetic effects -- meaning effects on the genome that don't directly change or mutate the DNA code of genes. Instead, what is altered is a chemical tag, or mark (Jirtle compares them to stop signs) in front of the gene that controls whether it is turned on or off. Jirtle and others' recent pioneering work has revealed that these changes to a developing organism can be both permanent, and passed on to their offspring and their offsprings' offspring.

Now Jirtle's lab is also the first to test an environmental contaminant in this mouse model of epigenetic effects.

"We exposed the mothers to low levels of bisphenol A that were comparable to what humans are exposed to. We found that in that case, that the offspring coat color shifted toward yellow, " Jirtle explains, "which means that those marks that were placed in front of the agouti gene normally were not present when you exposed the mothers to bisphenol A.

"This is not a healthy type of an environment to have created within the genome. It tends to destabilize the genome when you have fewer of these marks or stop signs being placed into the developing embryo," he says.

Jirtle says the dose of bisphenol A that they added to the mothers' chow was five times lower than the known "no-effect" dose in mice. "So, it's significantly lower than what you already see -- no gross observable effects. No change in liver size, weight, pathology, any of that. We're five-fold below that," he explains. Acknowledging that it's very difficult to determine comparable doses in mice and people, he says, "It's surely not tremendously higher than what humans are exposed to."

Blocking the Bad

As the group wrote in Proceedings of the National Academy of Sciences, since their previous work had shown that dietary supplements like folic acid had the opposite effect-- increasing the number of stop signs-- "it was very obvious, then, it would be interesting and important to determine whether these nutrient supplements could block the negative effects that were occurring because of exposure to this environmental contaminant bisophenol A," says Jirtle.

Indeed, they found that folic acid or the soy component genistein could stop bisphenol A's effects. "And we brought back basically the amount of marks and stop signs placed on the genome to what you would see in an animal that hasn't been exposed to bisphenol A at all," he says.

But Jirtle cautions there's no research yet on which human genes may be targeted by either the chemical, or the supplements. "I don't want to give the impression that this means that we can alter or counteract all levels of environmental contaminants," he says. "It's possible, from what we can see now with this study, that we could potentially alter the negative effects of bisphenol A, possibly even on humans, by nutrient supplements. But there has to be a point at which there are too many environmental contaminants to block with these nutritional supplements."

He also points out that if people were to start taking large doses of folic acid or similar supplements, they could do themselves more harm than good. "These types of dose-responses have not yet been worked out," Jirtle says.

"The other point I want to make is that when it comes to looking at the marks and regulation of genes through these placing of stop signs, that the targets-- the genes that are important in giving rise to diseases-- can be very different in mice than they can be in humans. And all of these studies were done in mice, they were not done in humans. But what we can, I think, bring home, is the fact that bisphenol A reduces the number of methyl groups, or marks, that are placed on the genome early in development. What the targets are for example in humans presently is not known," he adds.

Jirtle calls researching all of these effects in people "absolutely critical."

"These types of compounds have never been assessed for their ability to put these marks on genes at the very earliest stage of development, which is where this whole process is most vulnerable," he says. He points out that, in this study, they exposed the mouse mothers to bisphenol A from two weeks before their pregnancy until after weaning. Since human babies continue developing after birth-- especially our brains-- Jirtle says it's possible the effect could be important for babies and toddlers, not just fetuses.

"If I was a woman planning to have a family or was pregnant, I would definitely limit exposure to bisphenol A," he commented.

Some companies are marketing products like baby bottles and sippy cups that are bisphenol A-free.

This research was published in PNAS Advance Online Publication, July 30, 2007, and was funded by the National Institutes of Health, and by the Department of Energy.